Higher Rates of Processed Pseudogene Acquisition in Humans and Three Great Apes Revealed by Long-Read Assemblies

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• LINE-1 retrotransposition of protein-coding mRNAs is active in human germline and somatic genomes.
• Previous studies relied on short-read data, limiting discovery of full-length retrocopies and flanking regions.
• Genome-wide comparisons of gene retrocopies between humans and great apes are scarce.

Purpose of the Study:

• To develop a more sensitive and accurate method for identifying processed pseudogenes using long-read assemblies.
• To discover novel processed pseudogenes absent from the human reference genome (GRCh38).
• To compare gene retrocopies across human individuals and between humans and great apes.

Main Methods:

• Utilized long-read sequencing assemblies for identifying processed pseudogenes.
• Developed a method capable of providing full-length retrocopy sequences and flanking regions.
• Analyzed data from 22 human individuals and genomes of chimpanzee, gorilla, and orangutan.

Main Results:

• Identified 40 processed pseudogenes not present in the human reference genome (GRCh38) from 22 individuals.
• Discovered 17 pseudogenes present in GRCh38 but absent in some individuals.
• Achieved a significantly higher discovery rate compared to previous short-read based studies.
• Provided an overview of lineage-specific retrocopies in chimpanzee, gorilla, and orangutan.

Conclusions:

• Long-read sequencing offers a superior approach for discovering processed pseudogenes and understanding retrotransposition.
• The findings highlight the dynamic nature of the human genome and ongoing genetic variation.
• This study provides valuable insights into human and great ape genome evolution through retrocopy analysis.